Placental Ischemia‐Induced T H 17 Cells Mediate the Pathophysiology Associated with Preeclampsia

Preeclampsia (PE) is associated with hypertension, inflammation, intrauterine growth restriction (IUGR), increased CD4 + T Helper 17 cells (T H 17s) and agonistic auto‐antibodies to the AT1 receptor (AT1‐AA). The objective of this study was to determine a role for T H 17s in mediating pathophysiology associated with PE using the reduced uterine perfusion pressure (RUPP) rat model of PE. On gestation day 12 (GD12) RUPP‐induced T H 17s were injected into normal pregnant (NP) rats; On GD19 blood pressure (MAP) was recorded, and blood and tissues were collected. One‐way ANOVA was used for statistical analysis. MAP increased from 99±2 in NP (n=8) to 128±4 in RUPP (n=9) and to 111±3 mmHg in NP+T H 17 (n=11; p<0.05). Placental and renal ROS increased from 238 and 411 RLU, respectively, in NP to 328 and 603 RLU in RUPP and to 339 and 833 RLU in NP+T H 17 (p<0.05). Importantly pup weight (gm) decreased significantly from 2.19 in NP to 1.91 in RUPP, and to 1.9 in NP+T H 17 (p<0.05). Adoptive transfer of T H 17s also increased inflammation: IL‐6 increased significantly from 27.5 pg/mL in NP to 62.2 pg/mL in RUPP and to 75.9 pg/mL in NP+T H 17 (p<0.5); IL‐17 increased from 0.5 pg/mL in NP to 1.29 pg/mL in RUPP and increased to 5.5 pg/mL in NP+T H 17 (p>0.05). AT1‐AA significantly increased from 0.1beats/min in NP to 16.82beats/min in RUPP and to 15.6beats/min in NP+T H 17. T H 17s induced hypertension, ROS, IUGR, inflammation, and AT1‐AA in pregnant rats, demonstrating the importance of T H 17s to mediate the pathophysiology associated with PE and their potential as a new therapeutic target for treatment of PE. NIH grants RO1HD067541 and T32HL105324